Abstract
BackgroundThe ubiquitous bacterial trans-translation is one of the most studied quality control mechanisms. Trans-translation requires two specific factors, a small RNA SsrA (tmRNA) and a protein co-factor SmpB, to promote the release of ribosomes stalled on defective mRNAs and to add a specific tag sequence to aberrant polypeptides to direct them to degradation pathways. Helicobacter pylori is a pathogen persistently colonizing a hostile niche, the stomach of humans.Principal FindingsWe investigated the role of trans-translation in this bacterium well fitted to resist stressful conditions and found that both smpB and ssrA were essential genes. Five mutant versions of ssrA were generated in H. pylori in order to investigate the function of trans-translation in this organism. Mutation of the resume codon that allows the switch of template of the ribosome required for its release was essential in vivo, however a mutant in which this codon was followed by stop codons interrupting the tag sequence was viable. Therefore one round of translation is sufficient to promote the rescue of stalled ribosomes. A mutant expressing a truncated SsrA tag was viable in H. pylori, but affected in competence and tolerance to both oxidative and antibiotic stresses. This demonstrates that control of protein degradation through trans-translation is by itself central in the management of stress conditions and of competence and supports a regulatory role of trans-translation-dependent protein tagging. In addition, the expression of smpB and ssrA was found to be induced upon acid exposure of H. pylori.ConclusionsWe conclude to a central role of trans-translation in H. pylori both for ribosome rescue possibly due to more severe stalling and for protein degradation to recover from stress conditions frequently encountered in the gastric environment. Finally, the essential trans-translation machinery of H. pylori is an excellent specific target for the development of novel antibiotics.
Highlights
Helicobacter pylori is a gram negative bacterial pathogen that infects the stomach of about half of the world population
We conclude to a central role of trans-translation in H. pylori both for ribosome rescue possibly due to more severe stalling and for protein degradation to recover from stress conditions frequently encountered in the gastric environment
We showed that residues necessary for ribosome rescue by SsrA are essential for H. pylori growth and that the tagging of trans-translated proteins is required for its adaptation to stressful conditions and for competence
Summary
Helicobacter pylori is a gram negative bacterial pathogen that infects the stomach of about half of the world population. Lifelong colonization of the gastric mucosa by H. pylori implies that this bacterium is well adapted to this hostile environment facing both permanent acid stress in the mucus layer and oxidative stress at the gastric epithelium due to the host’s immune response [2]. The mechanisms involved in the recovery from damages caused by the exposure to stress are critical in the adaptive response. These involve both active repair procedures (well studied for oxidative stress in H. pylori [3]) and quality control mechanisms. Helicobacter pylori is a pathogen persistently colonizing a hostile niche, the stomach of humans
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